A61K38/1777

COMPOSITIONS AND METHODS FOR TREATMENT OF GCASE RELATED DISEASE STATES
20200353042 · 2020-11-12 ·

Disclosed are compositions and methods of treating a neurodegenerative disease in an individual. The methods disclose administration of an Integrin 41, Very Late Antigen-4 positive neural precursor cell (VLA4+NPC) transfected with a lentivirus overexpressing wild type GCase to an individual having a neurodegenerative disorder. The neurodegenerative disease may include lipid storage diseases, for example Gaucher disease, Parkinson's disease (PD), Dementia with Lewy bodies.

POLYPEPTIDE NANOTUBES LINKED BY DISULFIDE BONDS FOR TARGETED DELIVERY OF CYTOTOXIC THERAPIES

Provided herein is a self-assembling polypeptide-based nanotube system having the ability to target cancer cells. The nanotubes target the cancer cell surface through integrin engagement with the help of multiple RGD units present along their surface and release their drug payload in a sustained manner. In addition, the nanotubes can be utilized for cellular imaging using any covalently tagged fluorescent dye. Provided herein is a self-assembling polypeptide-based nanotube system having the ability to target cancer cells. The nanotubes target the cancer cell surface through integrin engagement with the help of multiple RGD units present along their surface and release their drug payload in a sustained manner. In addition, the nanotubes can be utilized for cellular imaging using any covalently tagged fluorescent dye.

METHOD OF TREATING PEDIATRIC DISORDERS

The invention provides methods for treating pediatric inflammatory bowel disease patients using vedolizumab.

IMMUNOMODULATING CELL CIRCUITS

Provided herein are methods and compositions for dynamically controlling and targeting multiple arms of the immune system. Some aspects provide mesenchymal stem cells (MSCs) engineered to produce multiple effector molecules. In some instances, each effector molecule modulates a different cell type of the immune system or different functions of a cell. Also provided herein are methods of using the MSCs to treat or alleviate symptoms of inflammatory bowel disease (IBD), for example.

IMMUNOMODULATING CELL CIRCUITS

Provided herein are methods and compositions for dynamically controlling and targeting multiple arms of the immune system. Some aspects provide mesenchymal stem cells (MSCs) engineered to produce multiple effector molecules. In some instances, each effector molecule modulates a different cell type of the immune system or different functions of a cell. Also provided herein are methods of using the MSCs to treat or alleviate symptoms of inflammatory bowel disease (IBD), for example.

MODIFIED INTEGRIN POLYPEPTIDES, MODIFIED INTEGRIN POLYPEPTIDE DIMERS, AND USES THEREOF

Described herein are modified integrin and/or headpiece polypeptides, and crystallizable integrin polypeptide dimers comprising a modified integrin and/or headpiece polypeptide and a disulfide bond linking the two integrin headpiece polypeptide subunits. Methods for using the modified integrin and/or headpiece polypeptides and the integrin polypeptide dimers are also provided herein. For example, methods for characterizing integrin-ligand interaction and identifying integrin ligands are also provided herein. In some embodiments, the identified integrin ligands can be used as inhibitors of integrins.

MESENCHYMAL STEM CELLS AND PHARMACEUTICAL COMPOSITION
20200016211 · 2020-01-16 · ·

The purpose of the present invention is to provide a mesenchymal stem cell that is highly safe when used as a medicine. The present invention is a mesenchymal stem cell characterized in that the Tissue Factor (TF) is expressed at low levels. Furthermore, the present invention includes a mesenchymal stem cell characterized in that at least one integrin gene selected from the group consisting of ITGA11, ITGA1, ITGB5, ITGBL1, ITGB1 and ITGAV is expressed at low levels. Furthermore, the present invention includes a mesenchymal stem cell characterized in that at least one integrin gene selected from the group consisting of ITGA4, ITGA9, ITGA7, and ITGA10 is expressed at high levels. It is preferable that the mesenchymal stem cell is allogeneic and is derived from a fatty tissue. The present invention also includes a pharmaceutical composition containing the mesenchymal stem cell.

FUSED IN SARCOMA (FUS) NUCLEAR TRANSLOCATION INHIBITORS FOR PREVENTING FIBROSIS

Disclosed herein are compositions and methods for inhibiting collagen production mediated by the Fused in Sarcoma (FUS) ribonucleoprotein. As disclosed herein, the C terminal domain of FUS contains an uncommon nuclear localization sequence (NLS) motif called PY-NLS that binds the nuclear import receptor transportin. Phosphorylation of FUS leads to its association with transportin and nuclear translocation with consequent increased in collagen production. Therefore, disclosed herein is an isolated peptide having a transportin-binding moiety, which inhibits FUS from binding transportin, linked to a membrane translocating motif. These compositions and methods can be used to inhibit FUS-mediated collagen production, and treat fibrotic disease involving FUS-mediated collagen accumulation in kidneys and other organs displaying fibrotic diseases.

MODIFIED INTEGRIN POLYPEPTIDES, MODIFIED INTEGRIN POLYPEPTIDE DIMERS, AND USES THEREOF

Described herein are modified integrin ? and/or ? headpiece polypeptides, and crystallizable integrin polypeptide dimers comprising a modified integrin ? and/or ? headpiece polypeptide and a disulfide bond linking the two integrin headpiece polypeptide subunits. Methods for using the modified integrin ? and/or ? headpiece polypeptides and the integrin polypeptide dimers are also provided herein. For example, methods for characterizing integrin-ligand interaction and identifying integrin ligands are also provided herein. In some embodiments, the identified integrin ligands can be used as inhibitors of integrins.

ALPHA(V)BETA(6) INTEGRIN-BINDING PEPTIDES AND METHODS OF USE THEREOF

The present invention provides peptide conjugates that target an integrin such as .sub.v.sub.6 integrin. In particular embodiments, the peptide conjugates comprise a moiety such as a PEG moiety, an imaging agent, or a therapeutic agent. The peptide conjugates of the present invention are particularly useful for imaging a tumor, organ, or tissue. Compositions and kits containing the peptide conjugates of the present invention are also provided herein.